The Shope papilloma-carcinoma system has great potential in definition of basic biochemical phenomena which are critical to the neoplastic process. This is so since in domestic and cottontail rabbits there is a viral induced progression from normal skin yields papilloma yields carcinoma. We have shown that multiple copies of the viral genome are conserved in all neoplasms and that some 5% of viral genetic information is transcribed in tumors of domestic rabbits (which characteristically do not produce virus). That multiple copies of the virus genome are present in viral superinfected chemically induced papillomas and in serially transplantable VX-2 and VX-7 carcinomas has also been shown. In the present application we propose to determine: 1) Whether the same transcripts are present in all tumors, 2) Whether or not the viral DNA is covalently integrated into the host cell genome, 3) If there is a translation product in these tumors and if so, its basic properties (since it is likely to be involved in an induction and maintenance of the neoplastic state ), 4) The viral specific macromolecular events which accompany malignant change induced by the virus in superinfected papillomas established by a chemical carcinogen. In addition, in related studies the effect of a tumor promotor on the expression of viral genes will be assessed, 5) If VX-2 and VX-7 carcinomas resemble the primary tumors with respect to viral gene expression. Should this prove to be the case, cultures of these cells will be intensively studied to determine the nature of the virus cellular relationship as it relates to these neoplastic cells, 6) If using additional methods, cell lines from the virus tumors can be established in vitro. Molecular hybridization, restriction endonuclease digestion, immunoprecipitation of radioactive materials and cell culture methods appropriate to epidermal cells will be the primary tools employed in these studies.